The gold standard for any new therapy in the U.S. is approval by the Food and Drug Administration (FDA). This approval clears the therapy for sale and often also means it will be covered by insurance. But along the way there are other designations that can mean a lot to a company developing a new approach to a deadly disease.
That’s what recently happened with Mustang Bio’s MB-107. The therapy was given Orphan Drug Designation for the treatment of X-linked Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease”, a rare but deadly immune disorder affecting children. This is the same therapy that CIRM is funding in a clinical trial we’ve blogged about in the past.
Getting Orphan Drug Designation can be a big deal. It is given to therapies intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. It comes with some sweet incentives, such as tax credits toward the cost of clinical trials and prescription drug user fee waivers. And, if the product becomes the first in its class to get FDA approval for a particular disease, it is entitled to seven years of market exclusivity, which is independent from intellectual property protection.
This is not the first time Mustang Bio’s MB-107 has been acknowledged as a potential gamechanger. It’s also been given three other classifications both here in the US and in Europe.
Rare Pediatric Disease Designation: this also applies to treatments for diseases affecting fewer than 200,000 people in the US that have the potential to provide clinically meaningful benefits to patients. It provides the company with a “voucher” that they can use to apply for priority review for another therapy they are developing. The hope is that this will encourage companies to develop treatments for rare childhood diseases that might not otherwise be profitable.
Regenerative Medicine Advanced Therapy (RMAT) designation: this allows for faster, more streamlined approvals of regenerative medicine products
Advanced Therapy Medicinal Product classification: this is granted by the European Medicines Agency (EMA) to medicines that are based on genes, tissues or cells and can offer groundbreaking opportunities for the treatment of disease.
Of course, none of these designations are a guarantee that Mustang Bio’s MB-107 will ultimately get FDA approval, but they’re a pretty good indication that a lot of people have confidence they’ll get there.
What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.
Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.
The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?
It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.
We’ll hear what’s being done to find therapies for
Rare diseases that affect children
Type 1 diabetes
We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.
It’s going to be a fascinating day. And did I mention it’s free!
You can’t look at this photo and not smile. This is Evie Vaccaro, and it’s clear she is just bursting with energy and vitality. Sometimes it feels like I have known Evie all her life. In a way I have. And I feel so fortunate to have done so, and that’s why this photo is so powerful, because it’s a life that almost ended before it had a chance to start.
Evie was born with a rare condition called Severe Combined Immunodeficiency (SCID). Children with this condition lack a functioning immune system so even a simple cold or diaper rash can prove fatal. Imagine how perilous their lives are in a time of COVID-19. These children used to be called “bubble babies” because they were often kept inside sterile plastic bubbles to keep them alive. Many died before their second birthday.
Today there is no need for plastic bubbles. Today, we have a cure. That’s a word we use very cautiously, but in Evie’s case, and the case of more than 40 other children, we use it with pride.
Dr. Don Kohn at UCLA has developed a method of taking the child’s own blood stem cells and, in the lab, inserting a corrected copy of the gene that caused SCID, and then returning those cells to the child. Because they are stem cells they multiply and renew and replicate themselves, creating a new blood supply, one free of the SCID mutation. The immune system is restored. The children are cured.
This is a story we have told several times before, but we mention it again because, well, it never gets old, and because Evie is on the front and back cover of our upcoming Annual Report. The report is actually a look back on the last 18 months in CIRM’s life, reporting on the progress we have made in advancing stem cell research, in saving and changing lives, and in producing economic benefits for California (billions of dollars in sales revenue and taxes and thousands of jobs).
Evie’s story, Evie’s photo, is a reminder of what is possible thanks to the voters of California who created CIRM back in 2004. Hers is just one of the stories in the report. I think, you’ll enjoy reading all of them.
Like many kids, let’s face it, many adults too, Ronav “Ronnie” Kashyap is getting a little bored stuck inside all day during the coronavirus pandemic. This video, shot by his dad Pawash, shows Ronnie trying to amuse himself by pretending to be hard at work.
In Ronnie’s case he was rushed to UC San Francisco shortly after his birth when a newborn screening test showed he had SCID. He spent the next several months there, in isolation with his parents, preparing for the test. Doctors took his own blood stem cells and, in the lab, corrected the genetic mutation that causes SCID. The cells were then re-infused into Ronnie where they created a new blood supply and repaired his immune system.
How good is his immune system today? Last year his parents, Upasana and Pawash, were concerned about taking Ronnie to a crowded shopping mall for fear he might catch a cold. Their doctor reassured them that he would be fine. So, they went. The doctor was right, Ronnie was fine. However, Upasana and Pawash both caught colds!
Just a few weeks ago Ronnie started pre-school. He loves it. He loves having other kids to play with and his parents love it because it helps him burn off some energy. But they also love it because it showed Ronnie is now leading a normal life, one where they don’t have to worry about everything he does, every person he comes into contact with.
Sounds a bit like how the rest of us are living right now doesn’t it. And the fears that Ronnie’s parents had, that even a casual contact with a friend, a family member or stranger, might prove life-threatening, are ones many of us are experiencing now.
When Ronnie was born he faced long odds. At the time there were only a handful of scientists working to find treatments for SCID. But they succeeded. Now, Ronnie, and all the other children who have been helped by this therapy are living proof that good science can overcome daunting odds to find treatments, and even cures, for the most life-threatening of conditions.
Today there are thousands, probably tens of thousands of scientists around the world searching for treatments and cures for COVID-19. And they will succeed.
Till then the rest of us will have to be like Ronnie. Stay at home, stay safe, and enjoy the luxury of being bored.
Problems with blood stem cells, a type of stem cell in your bone marrow that gives rise to various kinds of blood cells, can sometimes result in blood cancer as well as genetic and autoimmune diseases.
It is because of this that researchers have looked towards blood stem cell transplants, which involves replacing a person’s defective blood stem cells with healthy ones take from either a donor or the patient themselves.
However, before this can be done, the existing population of defective stem cells must be eradicated in order to allow the transplanted blood stem cells to properly anchor themselves into the bone marrow. Current options for this include full-body radiation or chemotherapy, but these approaches are extremely toxic.
But what if there was a way to selectively target these blood stem cells in order to make the transplants much safer?
An article published in Nature highlights the advancements made in the field of blood stem cell transplantation, some of which is work that is funded by yours truly.
The article discusses how Forty Seven tested two antibodies in monkeys. One antibody blocks the activity of a molecule called c-Kit, which is found on blood stem cells. The other is the antibody that blocks CD47, which is found on some immune cells. Inhibiting CD47 allows those immune cells to sweep up the stem cells that were targeted by the c-Kit antibody, thereby boosting its effectiveness. In early tests, the two antibodies used together reduced the number of blood stem cells in bone marrow. The next step for this team is to demonstrate that the treatment clears out the old supply of stem cells well enough to allow transplanted cells to flourish.
Another notable segment of this article is the CIRM funded trial that is being conducted by Dr. Judith Shizuru at Stanford University. This clinical trial also uses an antibody that targets c-Kit found on blood stem cells.
The purpose of this trial is to wipe out the problematic blood stem cells in infants with X-linked Severe combined immunodeficiency (SCID), a rare fatal genetic disorder that leaves infants without a functional immune system, in order to introduce properly functioning blood stem cells. Dr. Shizuru and her team found that transplanted blood stem cells, in this case from donors who did not have the disease, successfully took hold in the bone marrow of four out of six of the babies.
You can read more about Dr. Shizuru’s work in a previous blog post as well.
satisfying to see two projects you have supported for a long time do well. That’s
particularly true when the projects in question are targeting conditions that
have no other effective therapies.
This week we learned
that a clinical trial we funded to help people with spinal cord injuries
continues to show benefits. This trial holds a special place in our hearts
because it is an extension of the first clinical trial we ever funded.
Initially it was with Geron,
and was later taken up by Asterias
Biotherapeutics, which has seen been bought by Lineage Cell Therapeutics Inc.
The therapy involved transplanting oligodendrocyte progenitor cells (OPCs), which are derived from human embryonic stem cells, into people who suffered recent spinal cord injuries that left them paralyzed from the neck down. OPCs play an important role in supporting and protecting nerve cells in the central nervous system, the area damaged in a spinal cord injury. It’s hoped the cells will help restore some of the connections at the injury site, allowing patients to regain some movement and feeling.
In a news
release, Lineage said that its OPC
therapy continues to report positive results, “where the overall safety profile
of OPC1 has remained excellent with robust motor recovery in upper extremities
maintained through Year 2 patient follow-ups available to date.”
Two years in the
patients are all continuing to do well, and no serious unexpected side effects
have been seen. They also reported:
– Motor level improvements
Five of six Cohort 2 patients achieved
at least two motor levels of improvement over baseline on at least one side as
of their 24-month follow-up visit.
In addition, one Cohort 2 patient
achieved three motor levels of improvement on one side over baseline as of the
patient’s 24-month follow-up visit; improvement has been maintained through the
patient’s 36-month follow-up visit.
Brian M. Culley, CEO of Lineage Cell Therapeutics called the news “exciting”, saying “To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence.”
The other good news came from Orchard Therapeutics, a company we have
partnered with on a therapy for Severe Combined Immunodeficiency (SCID) also
known as “bubble baby diseases” (we have blogged about this a lot including
In a news
release Orchard announced that the European Medicines Agency (EMA) has granted an accelerated
assessment for their gene therapy for metachromatic leukodystrophy (MLD). This
is a rare and often fatal condition that results in the build-up of sulfatides
in the brain, liver, kidneys and other organs. Over time this makes it harder
and harder for the person to walk, talk, swallow or eat.
Anne Dupraz-Poiseau, chief regulatory
officer of Orchard Therapeutics, says this is testimony to the encouraging
early results of this therapy. “We look forward to working with the EMA to
ensure this potentially transformative new treatment, if approved, reaches
patients in the EU as quickly as possible, and continuing our efforts to expand
patient access outside the EU.”
The accelerated assessment potentially
provides a reduced review timeline from 210 to 150 days, meaning it could be
available to a wider group of patients sooner.
An independent Economic Impact Report says the California Institute for Regenerative Medicine (CIRM) has had a major impact on California’s economy, creating tens of thousands of new jobs, generating hundreds of millions of dollars in new taxes, and producing billions of dollars in additional revenue for the state.
The report, done by Dan Wei and Adam Rose at the Price School of Public Policy at the University of Southern California, looked at the impacts of CIRM funding on both the state and national economy from the start of the Stem Cell Agency in 2004 to the end of 2018.
The total impacts on the California economy are estimated
billion of additional gross output (sales revenue)
million of additional state/local tax revenues
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs, half of which offer salaries
considerably higher than the state average
Millan, M.D., CIRM’s President and CEO, says the report reflects the Agency’s
role in building an ecosystem to accelerate the translation of important stem
cell science to solutions for patients with unmet medical needs. “CIRM’s
mission on behalf of patients has been the priority from day one, but this
report shows that CIRM funding brings additional benefits to the state. This report
reflects how CIRM is promoting economic growth in California by attracting
scientific talent and additional capital, and by creating an environment that
supports the development of businesses and commercial enterprises in the state”
In addition to the benefits to California, the impacts
outside of California on the US economy are estimated to be:
billion of additional gross output (sales revenue)
million of additional state (non-Californian) & local tax revenue
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs
researchers summarize their findings, saying: “In terms of economic impacts, the
state’s investment in CIRM has paid handsome dividends in terms of output, employment,
and tax revenues for California.”
The estimates in the report are based on the economic stimulus
created by CIRM funding and by the co-funding that researchers and companies
were required to provide for clinical and late-stage preclinical projects. The
estimates also include:
Investments in CIRM-supported projects from private funders such
as equity investments, public offerings and mergers and acquisitions,
Follow-on funding from the National Institutes of Health and other
organizations due to data generated in CIRM-funded projects
Funding generated by clinical trials held at CIRM’s Alpha Stem
Cell Clinics network
researchers state “Nearly half of these impacts emanate from the $2.67 billion
CIRM grants themselves.”
economic impact of California’s investment in stem and regenerative cell
research is reflective of significant progress in this field that was just
being born at the time of CIRM’s creation,” says Dr. Millan. “We fund the most
promising projects based on rigorous science from basic research into clinical
trials. We partnered with researchers and companies to increase the likelihood
of success and created specialized infrastructure such as the Alpha Clinics
Network to support the highest quality of clinical care and research standards
for these novel approaches. The
ecosystem created by CIRM has attracted scientists, companies and capital from outside
the state to California. By supporting promising science projects early on,
long before most investors were ready to come aboard, we enabled our scientists
to make progress that positioned them to attract significant commercial
investments into their programs and into California.”
think one of the greatest strengths of CIRM has been their focus on development
of new stem cell therapies that can become real medicines,” says UCLA and
Orchard Therapeutics’ Don Kohn, M.D. “This has meant guiding academic
investigators to do the things that may be second nature in
industry/pharmaceutical companies but are not standard for basic or clinical
research. The support from CIRM to perform the studies and regulatory
activities needed to navigate therapies through the FDA and to form alliances
with biotech and pharma companies has allowed the stem cell gene therapy we
developed to treat SCID babies to be advanced and licensed to Orchard
Therapeutics who can make it available to patients across the country.”
support has been instrumental to our early successes and our ability to rapidly
progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says
Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at
Forty Seven Inc. “ CIRM was an early collaborator in our clinical
programs, and will continue to be a valued partner as we move forward with our
MDS/AML clinical trials.”
researchers say the money generated by partnerships and investments, what is
called “deal-flow funding”, is still growing and that the economic benefits
created by them are likely to continue for some time: “Deal-flow funding
usually involves several waves or rounds of capital infusion over many years,
and thus is it expected that CIRM’s past and current funding will attract
increasing amounts of industry investment and lead to additional spending
injections into the California economy in the years to come.”
They conclude their report by saying: “CIRM has led to
California stem cell research and development activities becoming a leader
among the states.”
There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.
In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.
In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”
Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.
There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.
The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.
In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:
“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”
A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.
That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.
Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.
The recent agreement transferring GSK’s rare disease gene therapies to Orchard Therapeutics was good news for both companies and for the patients who are hoping this research could lead to new treatments, even cures, for some rare diseases. It was also good news for CIRM, which played a key role in helping Orchard grow to the point where this deal was possible.
“At CIRM, our value proposition is centered around our ability to advance the field of regenerative medicine in many different ways. Our funding and partnership has enabled the smooth transfer of Dr. Kohn’s technology from the academic to the industry setting while conducting this important pivotal clinical trial. With our help, Orchard was able to attract more outside investment and now it is able to grow its pipeline utilizing this platform gene therapy approach.”
Under the deal, GSK not only transfers its rare disease gene therapy portfolio to Orchard, it also becomes a shareholder in the company with a 19.9 percent equity stake. GSK is also eligible to receive royalties and commercial milestone payments. This agreement is both a recognition of Orchard’s expertise in this area, and the financial potential of developing treatments for rare conditions.
Dr. Millan says it’s further proof that the agency’s impact on the field of regenerative medicine extends far beyond the funding it offers companies like Orchard.
“Accelerating stem cell therapies to patients with unmet medical needs involves a lot more than just funding research; it involves supporting the research at every stage and creating partnerships to help it fulfill its potential. We invest when others are not ready to take a chance on a promising but early stage project. That early support not only helps the scientists get the data they need to show their work has potential, but it also takes some of the risk out of investments by venture capitalists or larger pharmaceutical companies.”
CIRM’s early support helped UCLA’s Don Kohn, MD, develop a stem cell therapy for severe combined immunodeficiency (SCID). This therapy is now Orchard’s lead program in ADA-SCID, OTL-101.
Sohel Talib, CIRM’s Associate Director Therapeutics and Industry Alliance, says this approach has transformed the lives of dozens of children born with this usually fatal immune disorder.
“This gene correction approach for severe combined immunodeficiency (SCID) has already transformed the lives of dozens of children treated in early trials and CIRM is pleased to be a partner on the confirmatory trial for this transformative treatment for patients born with this fatal immune disorder.”
Dr. Kohn, now a member of Orchard’s scientific advisory board, said:
“CIRM funding has been essential to the overall success of my work, supporting me in navigating the complex regulatory steps of drug development, including interactions with FDA and toxicology studies that enhanced and helped drive the ADA-SCID clinical trial.”
CIRM funding has allowed Orchard Therapeutics to expand its technical operations footprint in California, which now includes facilities in Foster City and Menlo Park, bringing new jobs and generating taxes for the state and local community.
Mark Rothera, Orchard’s President and CEO, commented:
“The partnership with CIRM has been an important catalyst in the continued growth of Orchard Therapeutics as a leading company transforming the lives of patients with rare diseases through innovative gene therapies. The funding and advice from CIRM allowed Orchard to accelerate the development of OTL-101 and to build a manufacturing platform to support our development pipeline which includes 5 clinical and additional preclinical programs for potentially transformative gene therapies”.
Since CIRM was created by the voters of California the Agency has been able to use its support for research to leverage an additional $1.9 billion in funds for California. That money comes in the form of co-funding from companies to support their own projects, partnerships between outside investors or industry groups with CIRM-funded companies to help advance research, and additional funding that companies are able to attract to a project because of CIRM funding.
Ronnie Kashyap, patient in SCID clinical trial: Photo Pawash Priyank
More than 35 million people around the world have been killed by HIV, the virus that causes AIDS. So, it’s hard to think that the same approach the virus uses to infect cells could also be used to help children battling a deadly immune system disorder. But that’s precisely what researchers at UC San Francisco and St. Jude Children’s Research Hospital are doing.
The disease the researchers are tackling is a form of severe combined immunodeficiency (SCID). It’s also known as ‘bubble baby’ disease because children are born without a functioning immune system and in the past were protected from germs within the sterile environment of a plastic bubble. Children with this disease often die of infections, even from a common cold, in the first two years of life.
The therapy involves taking the patient’s own blood stem cells from their bone marrow, then genetically modifying them to correct the genetic mutation that causes SCID. The patient is then given low-doses of chemotherapy to create space in their bone marrow for the news cells. The gene-corrected stem cells are then transplanted back into the infant, creating a new blood supply and a repaired immune system.
Unique delivery system
The novel part of this approach is that the researchers are using an inactivated form of HIV as a means to deliver the correct gene into the patient’s cells. It’s well known that HIV is perfectly equipped to infiltrate cells, so by taking an inactivated form – meaning it cannot infect the individual with HIV – they are able to use that infiltrating ability for good.
The researchers say seven infants treated and followed for up to 12 months, have all produced the three major immune system cell types affected by SCID. In a news release, lead author Ewelina Mamcarz, said all the babies appear to be doing very well:
“It is very exciting that we observed restoration of all three very important cell types in the immune system. This is something that’s never been done in infants and a huge advantage over prior trials. The initial results also suggest our approach is fundamentally safer than previous attempts.”
If the stem cell-gene therapy combination continues to show it is both safe and effective it would be a big step forward in treating SCID. Right now, the best treatment is a bone marrow transplant, but only around 20 percent of infants with SCID have a sibling or other donor who is a good match. The other 80 percent have to rely on a less well-matched bone marrow transplant – usually from a parent – that can still leave the child prone to life-threatening infections or potentially fatal complications such as graft-versus-host disease.
CIRM is funding two other clinical trials targeting SCID. You can read about them here and here.